Pancreatic exocrine secretion is preciously regulated by hormonal and neural mechanisms. Although at least half of pancreatic exocrine secretion is controlled by neural mechanisms involving the vagus nerve, little is known about how it is regulated. The applicant's long term objective is to understand mechanisms of feedback control of centrally stimulated pancreatic secretion. Several recent discoveries from this laboratory and others have led us to hypothesize that he hormones pancreatic polypeptide (PP) and peptide YY (PYY) play an important role in feedback control of central (i.e. vagally mediated) pancreatic secretion: however, the mechanism is unknown. We hypothesize that a major point of control is the portion of the dorsal vagal complex that is outside the blood-brain barrier where these peptides have high affinity receptor and can act directly. Our aim is to systematically study centrally stimulated pancreatic secretion focusing on the dorsal vagal complex through microinfusion techniques and receptor autoradiography. An understanding of these mechanisms may be very important for defining basic principles of gut-brain interactions and regulations. These studies may lead to new theories on the etiology of various pancreatic disorders including idiopathic and a alcoholic pancreatitis. In addition, understanding these mechanism may lead to new therapies for resting the pancreas in acute pancreatitis or treating the cause of pain in chronic pancreatitis.